CONCLUSION

by admin on September 27, 2010

Lactoferrin is a prominent component of the mucosal defense system whose expression is upregulated in response to inflammatory stimuli. The protein contributes to mammalian host defense by acting as both an antibacterial and anti-inflammatory agent.

The anti-inflammatory activity occurs through inhibition of binding of lipopolysaccharide endotoxin to inflammatory cells, as well as through interaction with epithelial cells at local sites of inflammation to inhibit inflammatory cytokine production.

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The observation that lactoferrin can inhibit local inflammation by inhibition of TNF-_ mediated immune responses predicts that lactoferrin exerts a similar antiinflammatory role at local sites of immune defense where the protein is expressed (e.g., the gastrointestinal tract, lung, uterus, etc).

In this regard, the allergen induced cutaneous inflammation model used in the dermal studies described below is mechanistically similar to that observed in Crohn’s disease in humans [74,75], and mimicked by TNBS induced colitis in mice [76,77] both of which are mediated by Th1 cell dependent inflammatory responses.

Consistent with the hypothesis that lactoferrin may play an important role in modulation of gastric inflammation, the protein is expressed in the gastric mucosa of the stomach [78,79] and interacts with receptors localized on gastric intestinal epithelial cells.

Further, the expression of lactoferrin is elevated in the feces of patients with inflammatory conditions including ulcerative colitis and Crohn’s disease [32–34].

Several recent studies carried out in mice have shown that administration of lactoferrin can reduce gastritis induced by Helicobacter felis [80] and protect gut mucosal integrity during lipopolysaccharide-induced endotoxemia [81,82].

While results from human clinical trials to address the efficacy of the protein in regulation of gut inflammatory conditions have not yet been reported, the availability of recombinant human lactoferrin, together with the recently obtained positive results regarding the safety of orally delivered recombinant protein in phase 1 clinical trials [72,83], indicate that efficacy testing is indeed imminent.

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INFLUENCE OF LACTOFERRIN ON CUTANEOUS INFLAMMATION IN HUMANS

September 27, 2010

The preclinical studies summarized below predicted that topical administration of lactoferrin to humans may influence the development of cutaneous inflammatory reactions. In order to determine whether the inhibitory activity of lactoferrin on LC migration observed in the mouse also extended to human allergenic skin reactions, a similar study was carried out in human volunteers using […]

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LACTOFERRIN INHIBITS ALLERGEN INDUCED CUTANEOUS IMMUNITY

September 27, 2010

To test the hypothesis that lactoferrin may regulate local TNF-_ dependent inflammatory responses in an LPS independent manner, we recently used a mouse model of allergen induced skin inflammation [61]. Previous studies indicate that solvent allergens act as potent stimulators of cutaneous immunity.  Upon topical administration of a solvent allergen such as oxazolone, hapten-primed epidermal […]

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REGULATION OF IMMUNE RESPONSES BY LACTOFERRIN

September 27, 2010

A significant body of evidence has accumulated in recent years to support a role for lactoferrin in regulation of host immunity [28,29]. Lactoferrin is expressed in neutrophil secondary granules [5] and has been reported to have both positive [50] and negative [27,51-53] regulatory effects on myelopoiesis. Systemic infection with bacteria is accompanied by a rapid […]

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ANTIBACTERIAL PROPERTIES OF LACTOFERRIN

September 27, 2010

The antibacterial functions of lactoferrin have been substantiated by both in vitro [37–39] and in vivo [40,41] evidence. It appears that two different mechanisms involving two separate domains of the protein contribute to the antimicrobial functions of lactoferrin. The first mechanism is a bacteriostatic effect related to the high iron binding affinity of the protein […]

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LACTOFERRIN: A KEY COMPONENT OF THE FIRST LINE OF HOST DEFENSE

September 27, 2010

Although originally identified as an abundant protein in milk secretions, lactoferrin is expressed predominantly by surface epithelia and secreted into the mucosal environment. Thus, the protein is produced at high levels in nasal and tracheal passages and in gastric, genital and ophthalmic secretions. These secretions contain a variety of broad range antimicrobial  and anti-inflammatory peptides […]

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LACTOFERRIN: A MEMBER OF THE TRANSFERRIN FAMILY OF IRON BINDING GLYCOPROTEINS

September 27, 2010

Lactoferrin is an iron binding glycoprotein that consists of a single polypeptide. It is the second most abundant protein in human milk [1,2] and is found in most exocrine secretions including tears, nasal secretions, saliva, intestinal mucus and genital secretions [3,4]. The protein also is expressed and secreted by the secondary granules of polymorphonuclear neutrophils […]

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